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Gabapentinoids

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Analgesia in Major Abdominal Surgery

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Abstract

Gabapentin and pregabalin are second-generation anticonvulsants that decrease release of excitatory neurotransmitters in spinal and supraspinal pathways by modulation of the N-type calcium channel. Although not licensed for the management of acute pain the use of gabapentin and pregabalin as adjuvants in the treatment of post-operative pain has been the subject of much interest. The effectiveness of peri-operative gabapentin in reducing acute post-operative pain and opioid consumption has been demonstrated in a number of studies. There is also increasing evidence of the effectiveness of pregabalin but there are fewer studies on which to draw conclusions. Thus, gabapentin and pregabalin are associated with ~10% reduction in post-operative pain at 24 h and 25–50% reduction in opioid consumption. The use of gabapentin and pregabalin is associated with a reduction in anxiety and opioid-related side effects, but conversely an increase in sedation, dizziness and visual disturbances (especially pregabalin). The appropriate dose and timing of administration remains uncertain although single dosing, whether before or after surgery, may be as effective as multiple dosing. However, it appears that higher doses may be more effective in reducing the incidence of persistent post-operative pain.

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References

  1. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Intern Med. 2006;166:1021–6.

    Google Scholar 

  2. Fukuda C, Kohler JC, Boon H, Austin Z, Krahn M. Prescribing gabapentin off label: perspectives from psychiatry, pain and neurology specialists. Can Pharm J. 2012;145:280–4.

    Article  Google Scholar 

  3. NHS England. Advice for prescribers on the risk of misuse of pregabalin and gabapentin. www.gov.uk/government/uploads/system/uploads/attachment_data/ file/385791/PHE-NHS_England_pregabalin_and_gabapentin_advice_Dec_2014.pdf.

  4. Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br J Anaesth. 2018;120:1315–34.

    Article  CAS  Google Scholar 

  5. Eroglu C, Allen NJ, Susman MW, et al. The gabapentin receptor α2δ-1 is the neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;139:380–92.

    Article  CAS  Google Scholar 

  6. Park S, Ahn ES, Han DW, Lee JH, Min KT, Kim H, Hong Y-W. Pregabalin and gabapentin inhibit substance P-induced NF-κB activation in neuroblastoma and glioma cells. J Cell Biochem. 2008;105:414–23.

    Article  CAS  Google Scholar 

  7. Gale JD, Houghton LA. Alpha 2 delta (α(2)δ) ligands, gabapentin and pregabalin: what is the evidence for potential use of these ligands in irritable bowel syndrome. Front Pharmacol. 2011;2:28.

    Article  Google Scholar 

  8. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661–9.

    Article  CAS  Google Scholar 

  9. Chen C, Cowles VE, Sweeney M. The intestinal absorption mechanism of gabapentin makes it appropriate for gastroretentive delivery. Curr Clin Pharmacol. 2013;8:67–72.

    CAS  PubMed  Google Scholar 

  10. Straube S, Derry S, Moore RA, Wiffen PJ, Mcquay HJ. Single dose gabapentin for established acute postoperative pain in adults. Cochrane Database Syst Rev. 2010;5:CD008183.

    Google Scholar 

  11. Hill CM, Balkenohl M, Thomas DW, Walker R, Mathé H, Murray G. Pregabalin in patients with postoperative dental pain. Eur J Pain. 2001;5:119–24.

    Article  CAS  Google Scholar 

  12. Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain: a systematic review of randomized controlled trials. Pain. 2006;126:91–101.

    Article  CAS  Google Scholar 

  13. Seib RK, Paul JE. Preoperative gabapentin for postoperative analgesia: a meta-analysis. Can J Anaesth. 2006;53:461–9.

    Article  Google Scholar 

  14. Tippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A syteamtic review of safety and efficacy. Anesth Analg. 2007;104:1545–56.

    Article  Google Scholar 

  15. Mathiesen O, Møiniche S, Dahl JB. Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol. 2007;7:6. Available at: www.biomedcentral.com/1471-2253/7/6.

    Article  Google Scholar 

  16. Peng PWH, Wijesundera DN, Li CCF. Use of gabapentin for perioperative pain control – a meta-analysis. Pain Res Manag. 2007;12:85–92.

    Article  CAS  Google Scholar 

  17. Moore RA, Straube S, Wiffen PJ, Derry S, Mcquay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;3:CD007076.

    Google Scholar 

  18. Engelman E, Cateloy F. Efficacy and safety of perioperative pregabalin for postoperative pain: a meta-analysis of randomized-controlled trials. Acta Anaesthesiol Scand. 2011;55:927–43.

    CAS  PubMed  Google Scholar 

  19. Zhang J, Ho KY, Wang Y. Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth. 2011;106:454–62.

    Article  CAS  Google Scholar 

  20. Dolemnan B, Heinink TP, Read DJ, Faleiro J, Lund JN, Williams JP. A systematic review and a meta-regression analysis of prophylactic gabapentin for postoperative pain. Anaesthesia. 2015;70:1186–204.

    Article  Google Scholar 

  21. Mishriky BM, Waldron NH, Habib AS. Impact of pregabalin on acute and persistent postoperative pain: a systematic review and a meta-analysis. Br J Anaesth. 2015;114:10–31.

    Article  CAS  Google Scholar 

  22. Eipe N, Penning J, Yazdi F, Mallick R, Turner L, Ahmadzai N, Ansari MT. Perioperative use of pregabalin for acute pain—a systematic review and meta-analysis. Pain. 2015;156:1284–300.

    Article  Google Scholar 

  23. Baidya DK, Agarwal A, Khanna P, Arora MK. Pregabalin in acute and chronic pain. J Anaesthesiol Clin Pharmacol. 2011;27:307–14.

    Article  CAS  Google Scholar 

  24. Weinbroum AA. Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Pharm Res. 2012;65:411–29.

    Article  CAS  Google Scholar 

  25. Chang CY, Challa CK, Shah J, Eloy JD. Gabapentin in acute postoperative pain management. Biomed Res Int. 2014;2014:631756. https://doi.org/10.1155/2014/631756.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Dahl JB, Nielson RV, Wettersley J, Nikolaisen L, Hamunen K, Kontinen VK, et al. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand. 2014;58:1165–81.

    Article  CAS  Google Scholar 

  27. Schug S, Goddard C. Recent advances in the pharmacological management of acute and chronic pain. Ann Palliat Med. 2014;3:263–75.

    PubMed  Google Scholar 

  28. Farrar JT, Berlin JA, Strom BL. Clinically important changes in acute pain outcome measures: a validation study. J Pain Symptom Manage. 2003;25:406–11.

    Article  Google Scholar 

  29. Cepeda MS, Africano JM, Polo R, Alcal R, Cepeda DB. What decline in pain intensity is meaningful to patients with acute pain? Pain. 2003;105:151–7.

    Article  Google Scholar 

  30. Dworkin RH, Turk DC, Wyrwich KW, Beeton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105–21.

    Article  Google Scholar 

  31. Schmidt PC, Ruchelli G, Mackey SC, Carroll IR. Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain. Anesthesiology. 2013;119:1215–21.

    Article  Google Scholar 

  32. Cheung CW, Choi WS, Leung YY, Lui F, Ng JK, Hei-Ho AM, Irwin MG. A double-blind randomized crossover study to evaluate the timing of pregabalin for third molar surgery under local anesthesia. J Oral Maxillofac Surg. 2012;70:25–30.

    Article  Google Scholar 

  33. Buvanendran A, Kroin JS, Kari M, Tuman KJ. Can a single dose of 300 mg of pregabalin reach acute antihyperalgesic levels in the central nervous system? Reg Anesth Pain Med. 2010;35:535–8.

    Article  CAS  Google Scholar 

  34. Buvanendran A, Kroin JS, Della Valle CJ, Morica M, Turman KJ. Cerebrospinal fluid neurotransmitter changes during the perioperative period in patients undergoing total knee replacement: a randomized trial. Anesth Analg. 2012;114:434–41.

    Article  CAS  Google Scholar 

  35. Gerbershagen HJ, Aduckathil S, van Wyck AJM, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013;118:934–44.

    Article  Google Scholar 

  36. White PF, Tufanogullari B, Taylor J, Klein K. The effect of pregabalin on preoperative anxiety and sedation levels: a dose-ranging study. Anesth Analg. 2009;108:1140–5.

    Article  CAS  Google Scholar 

  37. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijesundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg. 2012;115:428–42.

    Article  CAS  Google Scholar 

  38. Chaparro LE, Smith SA, Moore RA, Wiffen PJ, Gilron I. Pharmacotherapy for the prevention of chronic pain after surgery in adults. Cochrane Database Syst Rev. 2013;7:CD008307.

    Google Scholar 

  39. Saraswat V, Arora V. Preemptive gabapentin vs pregabalin for acute postoperative pain after surgery under spinal anaesthesia. Indian J Anaesth. 2008;52:829–34.

    Google Scholar 

  40. Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth. 2011;5:252–7.

    Article  Google Scholar 

  41. Bafna U, Rajarajeshwaran K, Khandelwal M, Verma AP. A comparison of effect of preemptive use of oral gabapentin and pregabalin for acute post-operative pain after surgery under spinal anesthesia. J Anaesthesiol Clin Pharmacol. 2014;30:373–7.

    Article  Google Scholar 

  42. Rajendran I, Basavareddy A, Meher BR, Srinivasan S. Prospective, randomised, double blinded controlled trial of gabapentin and pregabalin as pre emptive analgesia in patients undergoing lower abdominal and limb surgery under spinal anaesthesia. Indian J Pain. 2014;28:155–9.

    Article  Google Scholar 

  43. Ozgencil E, Yalcin S, Tuna H, Yorukoglu D, Kecik Y. Perioperative administration of gabapentin 1,200 mg day−1 and pregabalin 300 mg day−1 for pain following lumbar laminectomy and discectomy: a randomised, double-blinded, placebo controlled study. Singapore Med J. 2011;52:883–9.

    CAS  PubMed  Google Scholar 

  44. Schug SA, Palmer GM, Scott DA, Halliwell R, Trince J, editors. Acute pain management: scientific evidence. 4th ed. Melbourne: Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine; 2015. www.anzca.edu.au/resources/college-publications.

  45. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116:248–73.

    Article  Google Scholar 

  46. Eipe N, Penning J. Postoperative respiratory depression associated with pregabalin: a case series and a preoperative decision algorithm. Pain Res Manag. 2011;16:353–6.

    Article  Google Scholar 

  47. Cheng ZH, Frenk V, Bishop JD, Bowling T, Pass HA. Multimodality perioperative analgesia with paravertebral nerve block and gabapentin reduces narcotic use and hospital length of stay in mastectomy patients. Cancer Res. 2015;75(9 Suppl):P2-13-11.

    Article  Google Scholar 

  48. Siddiqui NT, Fischer H, Guerina L, Friedman Z. Effect of a preoperative gabapentin on postoperative analgesia in patients with inflammatory bowel disease following major bowel surgery: a randomized, placebo-controlled trial. Pain Pract. 2014;14:132–9.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Anaesthetics, St. George’s Hospital, London, UK

    Jeremy Cashman

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  1. Jeremy Cashman
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Correspondence to Jeremy Cashman .

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Editors and Affiliations

  1. Department of Anaesthetics and Critical Care, Royal Blackburn Hospital, Blackburn, Lancashire, UK

    Anton Krige

  2. Department of Anesthesiology and Critical Care, Virginia Commonwealth University Hospital, Richmond, VA, USA

    Michael J. P. Scott

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Cashman, J. (2018). Gabapentinoids. In: Krige, A., Scott, M. (eds) Analgesia in Major Abdominal Surgery. Springer, Cham. https://doi.org/10.1007/978-3-319-94482-1_4

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  • DOI: https://doi.org/10.1007/978-3-319-94482-1_4

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  • Online ISBN: 978-3-319-94482-1

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